Predicting survival and treatment response for liver cancer

28 October 2009

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A small RNA molecule, known as a microRNA, may help physicians identify liver cancer patients who, in spite of their poor prognosis, could respond well to treatment with a biological agent called interferon. The finding, by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, and their partners at Fudan University, Shanghai, and the University of Hong Kong in China and at Ohio State University, Columbus, appeared in the 8 October 2009, issue of the New England Journal of Medicine.

"Interferon is an experimental therapeutic agent that has been used for many years to treat cancer patients, but with modest benefit," said study first author Junfang Ji, PhD, of the Liver Carcinogenesis Section at NCI's Center for Cancer Research.

"Our findings are exciting because we are rediscovering a drug that may have great potential for patients with a particular genomic profile. Being able to treat patients with an existing drug based on a tumour's genomic profile should improve its efficacy and reduce the cost of treatment," added study senior author Xin Wei Wang, PhD, chief of the Liver Carcinogenesis Section.

Hepatocellular carcinoma, or HCC, is a common type of liver cancer. Surgery is currently the most effective therapy for this disease, but only about 10 percent to 20 percent of patients are eligible for this option, and even among eligible patients the relapse rate is high. Post-operative (adjuvant) treatment with interferon often follows surgery in an attempt to prevent relapse in some patients, but this approach often fails as well.

How HCC develops is unclear. What is known is that it occurs more often in men than in women, and men tend to develop a more aggressive form of the disease. Differences in tumour biology and/or in the tumour microenvironment – the noncancerous tissue surrounding a tumour – may play a role.

Changes in microRNA levels have been noted in various human cancers, so a research team led by Wang looked at variation in the expression of microRNAs involved in HCC. These small RNA molecules play an important role in controlling gene activity by regulating a process known as translation. In translation, another type of RNA molecule, called a messenger RNA (mRNA), copies the genetic code stored within a gene and carries it to cellular structures called ribosomes and, once there, serves as a template to build the cell's proteins. There are many different types of microRNA, and a single microRNA species can affect the expression of many different proteins.

The team measured levels of microRNAs associated with both cancerous and normal tissue in men and women. The researchers analysed microRNA expression profiles from 241 surgery patients. By first comparing the microRNA profiles of normal liver tissue, and then comparing microRNAs in men and women, the researchers identified several microRNAs that were expressed more abundantly in normal female liver tissue. One of these, miR-26, was highly abundant and showed the greatest difference between the sexes, so it was chosen for further analysis.

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